Chemistry: electrical and wave energy – Apparatus – Electrolytic
Reexamination Certificate
2000-09-13
2003-02-18
Warden, Jill (Department: 1743)
Chemistry: electrical and wave energy
Apparatus
Electrolytic
C204S416000
Reexamination Certificate
active
06521109
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a device for detecting an analyte in a sample belonging to a class of devices known as chemically-sensitive field-effect transistors (CHEMFET's) which are of particular interest for biomedical and industrial applications.
BACKGROUND OF THE INVENTION
There is considerable interest in methods for detection, measuring and monitoring chemical properties of a sample. A sample can be a solid, solution, gas, vapor or a mixture of those. The chemical properties of the sample are determined by the analyte present in the sample, the analyte can be e.g. an electrolyte, a biomolecule or a neutral molecule.
Chemical sensors belonging to a class of devices known as Chemically Sensitive Field-Effect Transistors (CHEMFET's) are of particular interest for biomedical and industrial applications. Chemically sensitive field-effect transistors measure chemical properties of the samples to which the device is exposed. In a CHEMFET, the changes at the surface of the gate dielectric are detected via the modulations of the electric field in the channel of a field-effect transistor. Such chemical changes can be induced by e.g. the presence of ions in aqueous solutions, but also by the interaction of an electroinactive organic compound with a biological-sensing element in contact with the gate of the field-effect transistor. In this way, the concentration of ions or organic biomolecules (e.g. glucose, cholesterol, and the like) in aqueous solutions can be measured. One promising application of this type of device regards the monitoring of the cell metabolism for fundamental research or drug-characterization studies.
Among CHEMFET devices, the ion-sensitive field-effect transistors are best known. The concept of ion-sensitive field-effect transistor (ISFET) has been introduced by P. Bergveld in 1970 [P. Bergveld,
IEEE Trans. Biomed. Eng.,
BME-17, 1970, pp. 70]. It was demonstrated that when the metal gate of an ordinary MOSFET is omitted and the dielectric layer is exposed to an electrolyte, the characteristics of the transistor are affected by the ionic activity of the electrolyte. The schematic drawing of a classic ISFET is shown in FIG.
1
. The silicon substrate
1
of the device acts as current pathway between the source region
3
and the drain region
2
. Both regions are contacted by metal electrodes
5
. The dielectric layer
4
is covered with an ion-selective membrane
6
which is exposed to the solution
7
. The device is encapsulated with an encapsulating material
9
. Optionally, a reference electrode
8
can be present.
ISFET's have first been developed for pH and Na
+
activity detection in aqueous solutions (C. D. Fung, P. W. Cheung and W. H. Ko,
IEEE Trans. El. Dev.,
Vol. ED-33, No.1, 1986, pp.8-18). The cation-sensitivity of the device is determined by the ionization and complexation of the surface hydroxyl groups on the gate dielectric surface. ISFET devices for Ca
2+
, K
+
activity monitoring have also been fabricated. The sensitivity towards these ions is achieved by incorporating a sensitized plastic membrane (PVC) in contact with the gate dielectric. Therefore, these sensors detect changes in the charge of the membrane or in the transmembranar potential. Besides the use of CHEMFET devices for the determination of ions (ISFET), CHEMFET's have also been employed as enzyme-sensitive FET (ENFET's) for organic molecule detection or immuno-sensitive FET's (IMFET's) for immunochemicals (antigen, antibody) monitoring.
CHEMFET's exhibit important advantages over conventional chemically selective electrodes. Usually, CHEMFET's are fabricated with standard CMOS technology, which offers the advantages of miniaturization and mass production. In the biomedical field, there is an especially important area for the application of miniaturized sensors. The sensor is mounted in the tip of indwelling catheters, through which their feasibility for monitoring blood electrolytes and parameters has been demonstrated.
The fabrication method offers the additional benefit of the fabrication of multi-ion sensors and integration in smart sensors and sensor arrays. A further advantage of the use of CHEMFET is the logarithmic response of the potential in function of the analyte concentration. This type of response is interesting if a broad concentration range is investigated. Since the response of a CHEMFET device is initiated by the field-effect, this response is very fast compared to the response of conventional chemically sensitive electrodes. Up to now, all CHEMFET devices are based on silicon or silicon based materials.
However, there are some problems that so far have hampered the commercial applications of these devices. The most important problem of the CHEMFET is the drift of the device. Drift is typically characterized by a relatively slow, monotonic temporal change in the threshold voltage of the FET. As a result, an incorrect estimation of the chemical properties (e.g. ion activity) of the sample will be determined. This problem is more pronounced for determination of e.g. physiological ion activities or concentrations, where a high accuracy is required (e.g. blood electrolytes monitoring). Therefore, the use of silicon-based CHEMFET's in this kind of applications is very reduced. A further limiting factor for the use of CHEMFET devices is the higher manufacturing cost of these devices. For medical application, one is mostly interested in throw-away devices, which implies very cheap devices. For medical and pharmaceutical applications, devices which can be integrated in plastic materials, are most suitable.
For silicon-based CHEMFET, the integration in plastic material is not straightforward.
In the prior art, thin film transistors based on organic materials have been fabricated. Garnier (Gamier F., Hajlaoui R., Yassar A., Srivastava P., Science, 1994, Vol. 265, p 1684) proposes the use polymeric materials in a thin film transistor. The choice of polymeric materials is determined by the application of the device, i.e. as transistor.
Organic materials, and more especially polymeric materials, have already been used as sensitive parts in combination with a solid-state transducer (inorganic material) or as membranes for immobilization of biomolecules (e.g. enzymes) for specific interactions (G.
Harsányi, Polymer Films in Sensor Applications—Technology, Materials, Devices and Their Characteristics,
TECHNOMIC Publishing Co. Inc. Lancaster-Basel, 1995, p 53-92 and p 149-155; G. Bidan,
Sensors and Actuators B,
Vol 6, 1992, pp. 45-56). In the electroconducting conjugated polymers-based (ECP-based) chemical sensors, there is a direct interaction between the EPC layer and the analyte to detect. The detection mechanism is based on the ion exchange between the ECP layer and the sample. Therefore, a doped ECP layer is needed. A major disadvantage is the required electrochemical deposition of the conducting layer, because this deposition technique is rather difficult to control, which results in the deposition of layers with a lower uniformity and reproducibility. Moreover, the electrochemical deposition of doped conjugated polymeric layers also implies a more complicated, multi-step process. Besides this, due to the electropolymerization reactions, the electroconducting conjugated polymer layer is always p-doped, which means that only anions can be detected. Furthermore, the deposition process requires electrodes made of metallic material or glassy carbon.
SUMMARY OF THE INVENTION
One aim of the invention is to describe an improved device for detecting an analyte in a sample which combines the advantages of existing CHEMFET devices with advantageous properties such as low price, disposability, reduced drift of the device and suitability for biomedical and pharmaceutical applications.
In a first aspect of this invention, a device for detecting an analyte in a sample is provided including an active layer comprising at least a dielectric material, a source electrode and a drai
Baert Kris
Bartic Carmen
Poortmans Jef
Interuniversitair Microelektronica Centrum (IMEC vzw)
Knobbe Martens Olson & Bear LLP
Noguerola Alex
Warden Jill
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